Chiropractic and Metabolomics
FEATURE
Richard N. Olree
DC
Although we have been correcting it with spinal adjustment for 113 years, the spinal subluxation is not fully understood. Scientific research is not presently sophisticated enough to determine the neurophysiological impact that spinal subluxation has on our patients. Does that mean that we do not adjust our patients because it has not been proven? Absolutely not! I treat my patients as if each spinal adjustment has a virtually unlimited potential in improving their health. E=MC2.
The new view of the chiropractic subluxation is the ramification of the contents contained in cerebral spinal fluids as it pertains to the human genome. With 80% of immunity located in the intestines via the intestinal biome, the remaining 20% of immunity is the function of the cerebral spinal fluids’ ability to control the function of 11,434 gene activities (Chiropractic Metabolomic Handbook, available at Hillmanhealthfoods.com). The current thinking is there are about 22,000 functional genes in the human genome.
Chiropractic Moves into the Genetic Ages
The Human Metabolomic Database (HMDB) is a freely available electronic database containing detailed information about small-molecule metabolites found in the human body. There are a multitude of different databases that can be understood, such as breast milk, saliva, urine, and others.
Cerebral spinal fluid (CSF) is considered the third most abundant fluid in the human body. Today, it is still considered to be “salt water” by most intellectual standards, but it is far from “salt water,” as the study of metabolomics is working to change this perception.
As chiropractors, changes in the human spine brought on by the adjustment cause a change in the flow of CSF to the affected area that is being adjusted, as well as the rest of the human spine as it relates to CSF.
Pressure in the CSF is different from blood pressure. With blood pressure, 120/80 is considered the norm; added together and divided by two, the average pressure in the arterial system is 100 pounds per square inch (psi). Pressure in the spinal cord system, including the brain CSF, is 20 psi. Sixty-four nerves drain this fluid to the body that averages 0.3125 psi, all things being equal. That is not a lot of pressure, but with spinal misalignments, the pressure can change and back up, which causes changes
"The key to understanding the profound effects of a Chiropractic treatment lies in understand the effects of CSF."
in the hydrodynamics of the entire system.
The key to understanding the profound effects of a chiropractic treatment lies in understanding the effects of CSF. Cerebral spinal fluid contains 435 distinct substances, according to the database provided by The Metabolomics Innovation Centre (TMIC). TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada. It is a not-for-profit organization leading Canada’s national genomics strategy with $900 million in funding from the federal government. CSF is not just “salt water.” There will be, in the future, scientific
research showing this and the changes within CSF itself under different states of diseases. These are not mentioned in the article, but the core substances that stimulate brain health are contained in this article.
Stumbling across this database was an “eyes wide open” realization about what happens to the patient undergoing a “chiropractic treatment.” The database of components of CSF is large and startling in complexity. With all of the components of CSF in the database, research has shown all of the genes that can be changed from the altered movement of CSF.
With 435 distinct components in CSF, that can affect up to 15,595 genes of the human genome. The number of genes affected will constantly change as research continues to change every day. All of the information about genes was obtained from both the Metabolomic Database as well as Pubmed.gov.
Genomics to Biology: The human genome sequence provides foundational information that now will allow development of a comprehensive catalog of all of the genome ’ s components, determination of the function of all human genes, and deciphering of how genes and proteins work together in pathways and networks.
Genomics to Health: Completion of the human genome sequence offers a unique opportunity to understand the role of genetic factors in health and disease, and to rapidly apply that understanding to prevention, diagnosis, and treatment. This opportunity will be realized through such genomics-based approaches as identification of genes and pathways; determining how they interact with enviromuental factors in health and disease; more precise prediction of disease susceptibility; vitamin, amino acid, and minerals responses; early detection of illness; and development of entirely new therapeutic approaches (i.e., hair mineral tissue analysis).
Of the 11,425 genes involved, many genes overlap in function. When duplication is considered, more than 8,000 genes are utilized as a result in the function of CSF.
The human immune system is primarily the result of intestinal functions, where 80% of the immune system is located according to contemporary understanding. The other 20% of the immune system is the function of the CSF, which is the controlling aspect of all immunity.
CSF is replaced every eight hours, according to literature, and it is considered to be primarily produced by the choroid plexus to flow through the ventricular system to reach the subarachnoid space (SAS) of the:
1. Skull
2. Spinal column
An additional source of CSF is the interstitial fluid (ISF) from the brain tissue that is produced at the bloodbrain barrier and may account for around 10% of the total volume of CSF. Three layers of meninges surround the central nervous system (CNS):
1. The pia mater that covers the brain and spinal cord parenchyma
2. The arachnoid
3. The dura mater layers, which line the skull and vertebral canal
The CSF flows through the SAS between the pia mater, which is semipermeable, and the arachnoid, which forms a tight barrier to prevent flow into the dura mater. Within the CNS itself, lymphatic vessels are believed to be absent. Instead, a system of paravascular spaces (historically known as Virchow-Robin spaces but recently described as part of the “glymphatic system”) is thought to provide channels for the movement of fluid and solutes from the brain’s interstitial space to the CSF and vice versa.
Based upon work in the early part of the twentieth century, the predominant outflow of CSF from the SAS is expected to take place through arachnoid villi or granulations that project into the dural venous sinuses. These structures are described as a series of tubules within an outgrowth of arachnoid tissue that are continuous with the CSF of the SAS of the:
1. Cranium
2. Spine
They were initially believed to act as one-way valves for a pressure-driven flow from CSF to venous blood, but evidence from electron microscopy later indicated the presence of an intact barrier of endothelial cells. Extensive research has not led to a consensus on the exact mechanism for flow through arachnoid villi and granulations despite their widespread acceptance as the major outflow sites of CSF. Direct in vivo physiological evidence of their function is lacking.
Since an original report by Schwalbe in 1869, a large body of work in many different species has indicated a role for lymphatic vessels draining CSF in both:
1. Cranial
2. Spinal regions
Attempts to quantify the proportion of CSF drained by the lymphatic system using cannulation of deep cervical lymphatic vessels and radiolabeled tracers have indicated in some species, such as rabbit and sheep, that lymphatic vessels were responsible for around 30 to 50% of total outflow, with the remainder assumed to be drained through arachnoid villi. The outflow pathways were defined using tracers to be within sheaths around cranial nerves, with the cribriform plate route along olfactory nerves (that extends to lymphatic vessels in the nasal mucosa) deemed especially important. These sheaths enclose extensions of the SAS that project extracranially with the nerves through foramina of the skull. At these locations, it was suggested that there are pathways for tracers to penetrate the arachnoid membrane to reach:
1. Interstitial spaces
2. Directly to lymphatic vessels outside the skull
3. Outflow pathways present around spinal nerve roots to reach lymphatic vessels in epidural tissue
Two recent reports in mice have indicated that the dura mater of the CNS is endowed with a network of lymphatic vessels capable of draining CSF or brain interstitial fluid (ISF). However, this potential route for drainage of CSF is controversial in light of the existence of the arachnoid barrier between the SAS and the dura mater.
Thus, the current paradigm suggests a dual-outflow system for CSF to reach the blood circulation—one directly to venous blood through arachnoid projections and one indirectly through the lymphatic system. At this point, though, there is a lack of consensus on what the relative contribution for each of these outflow pathways is to total outflow of CSF. It is also not clear which pathways are most important in reaching the lymphatic system. These are key questions because a functioning lymphatic vascular system draining CSF and brain ISF could be essential for many aspects of neurology, including immune function and clearance of toxic proteins, such as amyloid beta. Since many neurological conditions are associated with the aging process, it is also critical to determine if lymphatic outflow of CSF is altered in aged conditions.
The contents of CSF can be broken down into various categories based on the number of genes that can be regulated through CSF.
Minerals are first in the list because CSF has been
proven to contain the following 44 minerals, which affect 7,041 genes and are measured in uM (millimeters):
Sodium 145,000 • Manganese 0.149 Boron 3,587 • Arsenic 0.106 Potassium 2,163 • Nickel 0.097 Calcium 1,047 • Chloride 0.06 Magnesium 954 • Tin 0.05 Phosphorus 520 • Beryllium 0.045 Aluminum 109 • Platinum 0.041 Bromide 29 • Palladium 0.036 Iodine 16 • Molybdenum 0.034 Lithium 10.383 • Lead 0.017 Iron 9.293 • Cesium 0.015 Copper 2.253 • C admium 0.015 Strontium 1.12 • Gallium 0.011 Titanium 0.648 • Cobalt 0.01 Gold 0.6 • Tungsten 0.008 Zinc 0.538 • Ruthenium 0.005 Rubidium 0.499 • Cerium 0.005 Vanadium 0.404 • Yttrium 0.004 Selenium 0.32 • Mercury 0.004 Zirconium 0.277 • Silver 0.0025 Chromium 0.247 • Tantalum 0.002 Barium 0.223 • Antimony 0.002
Second in the list are oils, fats, and fatty acids affecting 1,461 genes. The list is condensed since there are many similar but structurally different ones. The list follows in alphabetical order: arachidonic acid, arachidonylglycerol, azelaic acid, butyric acid, caprylic acid, DHOME, DiHETrE, docosahexaenoic acid, dodecanoic acid, EpETrE, EpOME, epoxy-5, 8, 11-eicosatrienoic acid, epoxyoctadecenoic acid, glycerol, glyoxylic acid, HETE, HODE, hydroxyeicosatetraenoic acid, hydroxyoctadecadienoic acid, isobutyric acid, isovaleric acid, linoleic acid, lysoPC, myristic acid, oleic acid, OxoODE, palmitic acid, palmitoleic acid, prostaglandin, sphingomyelin, stearic acid, thromboxane, and TriHOME.
The third category is amino acids, which can affect 1,129 genes. The following list is in alphabetical order: (R)-3-hydroxybutyric acid, (R)-3-hydroxyisobutyric
acid, (S)-3-hydroxyisobutyric acid, 1-methylhistamine, 1-methylhistidine, 2-oxoarginine, 3-hydroxyphenylacetic acid, 3-methoxytyrosine, 3-methyl-2-oxovaleric acid,
3-methylhistidine, 4-guanidinobutanoic acid, 4-hydroxyL-proline, 5-hydroxy-L-tryptophan, acetyl-L-aspartic acid, agmatine, alpha-ketoisovaleric acid, arginine vasopressin 1-8, beta-alanine, butyrylcarnitine, citrulline, creatine, creatinine, cysteinylglycine, D-alanine, D-lactic acid, D-serine, epsilon-(gamma-Ghitamyl)-lysine, gamma-aminobutyryl-lysine, gamma-glutamyl glutamine, glutathione, glycylproline, guanidinosuccinic acid, hippuric acid, histamine, homo-L-arginine, hydroxyphenyllactic acid, indoleacetic acid, kynurenic acid, kyotorphin, L-a-glutamyl-L-lysine, L-alanine, L-arginine, L-asparagine, L-aspartic, L-carnitine, L-cysteine, L-glutamic acid, L-glutamine, L-glycine, L-Histidine, L-Isoleucine, L-Leucine, L-Lysine, L-Methionine, L-Phenylalanine, L-Serine, L-threonine, L-tryptophan, L-tyrosine, Lvaline, methylimidazoleacetic acid, N(6)-methyllysine, N6,N6,N6-trimethyl-L-lysine, N-a-acetyl-L-arginine, N-acetylaspartylglutamic acid, ornithine, oxidized glutathione, picolinic acid, Pi-methylimidazoleacetic acid, pipecolic acid, prolylhydroxyproline, pyroglutamic acid, quinolinic acid, S-adenosylhomocysteine, S-adenosylmethioninamine, S-adenosylmethionine, sulfinoalanine, taurine, and thiocyanate.
The fourth category is hormones, which control 517 genes. The following list is arranged alphabetically: 3,
4-dihydroxybenzeneacetic acid, 3, 4-dihydroxyphenylglycol, 3-methoxytyramine, 4-hydroxybutyric acid, acetyl-N-formyl-5-methoxykynurenamine, allopregnanolone, androstenedione, androsterone, angiotensin II, cortisol, dehydroepiandrosterone, dihydrotestosterone, dopamine, epinephrine, estradiol, gamma-aminobutyric acid, homovanillic acid, hyaluronan, L-dopa, melatonin, metanephrine, norepinephrine, normetanephrine, oxytocin, pregnenolone, progesterone, serotonin, testosterone, vanylglycol, and vasopressin.
The fifth category is vitamins and vitamin-related genes affecting 387 genes. The list is alphabetical: 5-me-
thyltetrahydrofolic acid, acetylcholine, alpha-tocopherol, ascorbic acid, biotin, choline, cyanocobalamin, dihydrothymine, folic acid, glycerophosphocholine, L-cystathionine, L-kynurenine, methylcobalamin, myoinositol, nicotinic acid, pantothenic acid, phosphorylcholine, pyridoxal 5 ’-phosphate, pyruvic acid, riboflavin, thiamine, thiamine monophosphate, and thiamine pyrophosphate.
The sixth category is drugs that control 294 genes. The list is arranged alphabetically: acetaminophen, caffeine, cotinine, dextromethorphan, ethanol, ibuprofen, L-dopa, levofloxacin, methanol, quetiapine, theophylline, and valerylcamitine.
The seventh category is based on energy and sugars, which affect 169 genes. The list is arranged alphabetically: 1,5-anhydrosorbitol, D-fructose, D-galactose, Dmannose, D-ribose, D-threitol, D-xylulose, erythritol, galactitol, glucose, hyaluronic acid, L-arabinose, L-lactic acid, mannitol, N-acetylneuraminic acid, neuraminic acid, sorbitol, and xylitol.
The eighth category is based on DNA/RNA, which affect 150 genes. The list is arranged alphabetically: 2’-deoxyuridine, adenine, adenosine, dihydrouracil, hypoxanthine, spermidine, spermine, thymidine, uracil, ureidopropionic acid, and uridine.
The ninth category is based on citric acid with 141 genes involved. The list is arranged alphabetically: 2-ketobutyric acid, cis-aconitic acid, citric acid, fumaric acid, isocitric acid, L-malic acid, malic acid, malondialdehyde, oxalacetic acid, and succinic acid.
The tenth category consists of man-made by-products affecting 115 genes. The list is arranged alphabetically: 4-hydroxybenzoic acid, acetaldehyde, glycolic acid, hexanal, hydroxypropionic acid, imidazoleacetic acid, isopropyl alcohol, parathion, propanal, and propionic acid.
The eleventh category is waste products, which control 103 genes. The list is arranged alphabetically: (R)-3-hydroxybutyric acid, 2-aminobenzoic acid, 5-Hhydroxyindoleacetic acid, allantoin, dimethyl sulfoxide, dimethylsulfide, formic acid, guanidine, hippuric acid, homocarnosine, inosine, propylene glycol, trimethylamine, and urea.
The twelfth category is cholesterol, which controls 30 genes. The list is arranged alphabetically: 24-hydroxycholesterol, 27-hydroxycholesterol, 7alpha-hydroxycholesterol, 7-dehydrocholesterol, 7-ketocholesterol, 8-dehydrocholesterol, cholesterol, and provitamin-D - 7-dehydrocholesterol.
The thirteenth category is disorders of metabolisms, which has involved 29 genes. The list is arranged al-
phabetically: acetoacetic acid, D-2-hydroxyglutaric acid, glutaric acid, glyceric acid, ketoleucine, L-2-hydroxy glutaric acid, L-arabitol, methylmalonic acid, Phydroxyphenylacetic acid, succinic acid semialdehyde, and ureidoisobutyric acid.
The fourteenth category is on based heme, which controls 28 genes. Bilirubin is the only substance in this category.
The fifteenth category is based on white blood cells and controls 20 genes. The list is arranged alphabetically: 20-hydroxy-leukotriene B4, leukotriene B4, leukotriene C4, 12, 13-DHOME, and 11(R)-HETE.
In all of the above categories, only substances that have been associated with gene activities have been listed. For a complete list of substances, please see the book A
Chiropractor’s Metabolomic Handbook for Cerebral Spinal Fluid.
Reduced Lymphatic Outflow from CSF in Aged Mice
The incidence of Alzheimer’s disease, other dementias, and many other neurodegenerative diseases increases with age. Recently, a hypothesis for the development of these
disorders proposed that toxic proteins, such as amyloid beta and tau, may accumulate in the brain due to reduced clearance. Earlier studies have shown a reduced turnover of CSF and removal of labeled proteins, including amyloid beta, after ventricular-cisternal perfusion in aged rats. Tests show lymphatic outflow from CSF was reduced in aged mice and would be similar to prior observations of reduced peripheral lymphatic transport in aged mice.
In conclusion, the early days of the chiropractic profession thrived and survived upon results more than scientific proof, despite a conspiracy to eliminate the profession, resulting in the historic 1990 Wilk et al. versus AMA case in favor of chiropractic. Today, we have the ability to further understand how the adjustment works on a molecular level. Many different supplements and therapies are utilized in assisting the doctor of chiropractic to help their clients. One of the best ways to serve our patients is to do tests within our licensure for intestinal bacteria, viral pathogens (Epstein-Barr virus, cytomegalovirus), hair tissue biopsy, and “23andMe” to ascertain genetic activities, which are largely ignored for use. These types of tests should be routinely performed as needed, depending on what the physician is attempting the body to normalize.
In essence, it is illegal to be healthy in today’s modem (post-World War II) world because the suboptimal physical condition drives and funds the “sick-care industry.” A
healthy population would severely reduce the so-called “health industrial complex” (higher-learning institutions, companies, and hospitals) because they would be largely unnecessary. Many people have been legally refused when seeking an alternative approach to regain their health, especially with cancers. We can use the tests and new genetic information coming to light, combined with food guidance, herbs, minerals, technological therapies, and the chiropractic adjustment, to aid in optimizing our “innate intelligence” to regain and maintain cellular health. It is far easier to maintain health than to try to regain it. Our job as physicians (teacher) is to educate our clients to better care for themselves and not keep them coming to temporarily fix something, only to return.
You may not yet realize it, but a chiropractic adjustment is applying energy to the patient’s spine and, at the speed of light, you change their mass and wait to see the changes in the human genome. E=MC2.
Richard N. Olree, DC, is a 1981 graduate of Logan College of Chiropractic and has been in practice % at the same location in northern Michigan. Other Jv ^ books that Dr. Olree has authored or coauthored Mil include Minerals for the Genetic Code; Minerals for Tumor Suppressing Genes; An Amish Man’s Handy Guide to Minerals, Vitamins, and Food Supplementation; and Minerals for Acupuncture Meridians. Contact him at 989-742-4242 or [email protected].
